Estrogenic compounds and animal growth promoters



United States Patent 3,373,029 ESTRQGENIC COMPOUNDS AND ANIMAL GROWTH PROMOTERS Edward B. Hodge, Phil H. Hidy, and Herbert L. Wehrmeister, Terre Haute, Ind., assignors to Commercial Solvents Corporation, a corporation of Maryland N 0 Drawing. Continuation-impart of application Ser. No. 561,393, June 29, 1966. This application Mar. 3, 1367, Ser. No. 620,263

Claims. (Cl. 99-2) ABSTRACT OF THE DISCLOSURE RO 0 CH3 GEN A -(CHz)a where R is selected from the group consisting of hydro gen, lower alkyl and benzyl and A is a radical selected from the group consisting of -CH=CH- and -CH -CH and animal feeds containing growth prom-otin g amounts thereof.

This application is a continuationin-part of application Ser. No. 561,393, filed June 29, 1966, now abandoned.

The present invention relates tonew compounds and an object of the present invention is to provide compounds which exhibit estrogenic activity or aid in increasing the rate of growth in meat-producing animals, e.g., cattle, lamb and swine.

The compounds of this invention are illustrated by the formula:

C=O HO- \OH:OH (CH2)3 hereinafter referred to as the fermentation estrogenic substance (F.E.S.) by reaction thereof with sodium cyanide and a mineral acid, e.g., sulfuric, hydrochloric, etc., in :aqueous solution. The hydroxyl groups can be converted to ethers, e.g., methyl ethers, as taught in US. Patent 3,239,342. Compounds where R is benzyl are described in copending application Ser. No. 532,113, filed Mar. 7, 1966, and application Ser. No. 620,259, filed Mar. 3, 1967, now abandoned, and dihydro F.E.S. compounds are described in US. Patent 3,239,354. The compounds of this invention in addition to their own activity are useful intermediates in the production of F.E.S.' amines similar to those described in US. Patent 3,239,- 346 upon reduction, for example, with hydrogen and Raney nickel. Care must be taken in the production of these compounds since hydrogen cyanide is released.

per 100 pounds of feed of the 3,373,029 Patented Mar. 12, 1968 The compounds can also be administered to animals by any suitable method including oral and parenteral administrations. For example, the compound can be blended with ordinary feed containing nutritional values in an amount sufficient to produce the desired rate of growth and can thus be fed directly to the animals, or the compound can be suspended in a suitable injection suspension medium such as peanut oil and injected parenterally. The amount of compound fed to an animal, of course, varies depending upon the animal, desired rate of growth and the like.

When the new compounds are to be administered in feeds, an animal feed composition may be prepared containing the usual nutritionally-balanced quantities of carbohydrates, proteins, vitamins and minerals, together with the compound of the present invention. Some of these usual dietary elements are grains, such as ground grain and grain byproducts; animal protein substances, such as those found in fish meal and meat scraps, vegetable proteins like soybean oil meal or peanut oil meal; vitaminaceous materials, e.g., vitamin A and D mixtures; riboflavin supplements and other vitamin B complex members; and bone meal and limestone to provide minerals. A type of conventional feed material for use with cattle include alfalfa hay and ground corn cobs together with supplementary vitaminaceous substances if desired.

The following examples serve to illustrate the invention.

Example I F.E.S. is mixed with an aqueous solution of sodium cyanide and sulfuric acid is slowly added while the temperature is maintained at 10 to Q0" (1, to produce the cyanohydrin derivative.

C \CEN Example II Example IV Six head of cattle per pounds of feed of the compound of Example I and their rate of growth is improved.

Example V Six head of cattle are fed a daily ration of alfalfa hay and ground corn cobs containing from 5 to 20 ounces compound of Example III and their rate of growth is improved.

The following are specific examples of animal feed compositions of this invention useful forincreasing the rate of growth and feed efiiciency of young animals to market weight. n i

are fed a daily ration of alfalfa hay and ground corn cobs containing from..5 to 20 ounces Example VI For young beef cattle, i.e., calves to yearlings running to two year olds, each animal is given to 20 milligrams per day of the compound produced in Example I intimately admixed in about 18 to 22 pounds per head per day of a complete pelleted ration for about 180 days. The complete pelleted ration includes in addition to the compound of Example I the following:

Barley 5. percent 40-43 Molasses of dried beet pulp do 34.5-37.5 Alfalfa pellets do 8.0 Tallow do 2.5 Calcium carbonate do .30 Urea do .30 Phosphorus source do .40 Salt do .50 Molasses do 10.00 Trace mineral do 0.5 Vitamin A MMlU/ton 2-4 (NoTn: Milo or corn, for example, can be substituted for the barley.)

The compound of Example I is admixed with the above ingredients in a stationary blender or a feed mix truck in the following amounts in grams per ton to provide an appropriate complete pelleted feed with dosage levels ranging from 5 to 90 milligrams per head per day.

Grams/ton: Mg./head/day .5 5 1.0 2.0 4.0 40 8.0 80

These gram amounts are premixed with, for example, 10 pounds of soybean hulls prior to admixture with the other ingredients.

Example VIII For young swine, i.e., six week old pigs to about 100 pound pigs, each animal is given 5 to 20 milligrams per day of the compound of Example III intimately admixed in about 1 /2 to 5 /2. pounds per head per day of a grower ration until it reaches a weight of about 100 pounds. When the swine weigh between 90 and 125 pounds the feed is changed to one whereby each animal is given 20 to 50 milligrams per day of the compound of Example III intimately admixed in about 5 /2 to 10 pounds per head per day of a finisher ration until it reaches market weight of about 220 pounds. The grower and finisher ration includein addition to the. compound of Example III "the following:

The compound of Example 111 is admixed with the above ingredients in a blender in the following amounts in milligrams per pound to provide an appropriate feed with dosage levels ranging from 6 to 96 milligrams per head per day.

Mg./pound: Mg./head/day 2 6 4 12 8 24 16 48 Example VIII For 4 to 10 month old lambs Weighing 50 to 70 pounds, each animal is given 1 to 15 milligrams per day of the compound of Example I, intimately admixed in about 3 to 6 pounds per head per day of a complete ration for 30 to 90 days. The complete ration includes in addition to the compound of Example I the following:

Pounds 10 Finely ground corn cobs 630 Ground corn 600 Dehydrated alfalfa meal 300 Dried molasses 120 Soybean meal (44% protein) 300 15 Dicalcium phosphate 14 Trace mineral salt 17 Premix vitamin, mineral and antibiotic 19 The compound of Example I is admixed with the above 9 ingredients in a blender in the following amounts in milligrams per pound to provide an appropriate complete feed with dosage levels ranging from 1 to 15 milligrams per head per day.

Mg./pound: Mg./head/day Example IX For broilers, i.e., day old to four week old chicks, a grower feed is prepared for feeding to the chicks for the first four weeks and a finisher feed is prepared for feeding the four week old chicks for the last five weeks until they reachtmarket weight of two and a half to three pounds dressed. For each pound of weight gain, the chicks eat about 1.5 to 2 pounds of feed. Thus they eat about 1.5 pounds of feed during the first four weeks and about five pounds of feed during the next five weeks. During the course of this feeding schedule, each bird should receive a total of about 12 to 36 milligrams of the compound of Example 111 in the grower and finisher feed each of which includes in addition to the compound of Example III the following:

Grower Finisher (lbs.) (lbs.)

Grand Yellow Corn 1,000 1,200 Soybean Meal (44% Protein) 700 500 Fish Meal (60% Protein) 100 S0 Alfalfa Meal 50 50 Meat and Bone Scraps 0 30 Animal at 80 80 Dicalcium Phosphate. 35 40 Iodized Salt 10 10 Limestone 15 Premix Vitamins Trace Minerals and Antibiotics 10 10 It is claimed:

R-O (I) (IJH:

/UOCH-(CH2)3 0H C=N -'-(C z)a where R is selected from the group consisting of hydrogen, lower alkyl and benzyl and A is a radical selected from the group consisting of CH=CH-- and CH -CH 2,. The compound of claim 1 wherein A is The compound of claim 2 wherein R is hydrogen. The compound of claim 2 wherein R is lower alkyl. The compound of claim 2 wherein R is benzyl. The compound of claim 1 wherein A is The compound of claim 6 wherein R is hydrogen. The compound of claim 6 wherein R is lower alkyl.

9. The compound of claim 6 wherein R is benzyl.

No references cited.

A. LOUIS MONACELL, Primary Examiner. H. H. KLARE HI, Assistant Examiner. 

